Following the minority stress model as a framework, we examine the associations between racial and homosexual stigma, substance use, and sexual risk behavior among a respondent-driven sample of Latino gay and bisexual men and male-to-female transgender persons in Chicago and San Francisco (N = 643). We use structural equations to test such a model and disentangle the possible effects of the different stigmas and their corresponding dimensions (i.e., perception, experience, internalization). Findings revealed distinct pathways to sexual risk. Two are typified by experienced homosexual stigma and internalized racial stigma via multiple drug use, and two are characterized by experienced racial stigma and internalized homosexual stigma via alcohol use.